叶酸及其部分代谢相关分子与人类遗传稳定性初探

发布时间：2018-04-16 17:59

本文选题：叶酸 + 维生素B_(12)　；参考：《云南师范大学》2005年硕士论文

【摘要】：叶酸是人体正常发育的重要微营养物质,其涉及dUMP到dTMP的合成, 同时通过同型半胱氨酸(HC)合成蛋氨酸(Met)、S-腺苷蛋氨酸(SAM)的生化过程而影响DNA甲基化。因此,叶酸、维生素B_(12)(B_(12))缺乏以及Met/SAM 合成受阻,可引起dUMP积累并掺入DNA,从而导致各种DNA结构损伤;同时可影响细胞尤其DNA甲基化过程,从而影响基因表达、染色体分离。本研究以胞质阻断微核分析(CBMN)研究了叶酸对维护乳腺癌患者及其对照个体淋巴细胞基因组稳定性的作用及差异,并探讨了叶酸代谢途径中的重要分子Met、B_(12)缺乏对BRCAI突变的乳腺癌患者成淋巴细胞株及正常人成淋巴细胞株遗传毒性效应。研究首先从24例乳腺癌患者、30例正常人外周血中分离淋巴细胞,在含 30nM、120nM、240nM 叶酸的RPMI-1640 培养基中(8%透析小牛血清、100U 双抗、2mM谷氨酰胺、pH7.0)培养,第8天以细胞松弛素B(CB)阻断细胞质分裂,28小时后收获细胞,以CMBN分析叶酸缺乏对人类淋巴细胞产生的遗传毒性效应:为了证实Met、B_(12)对叶酸代谢和遗传稳定性的影响,试验还以15,50 μM 的Met与75～1200 pM B_(12)组合的12种RPMI-1640 培养基(8%透析小牛血清、 100U 双抗、2mM 谷氨酰胺、pH7.0),培养携带BRCAI,基因突变的乳腺癌患者成淋巴细胞株GM13705和正常人成淋巴细胞株GM12593,第8天以细胞松弛素 B(CB)阻断细胞质分裂,28小时后收获细胞,以CMBN分析Met、B_(12)对人类成淋巴细胞株基因组稳定性的影响。试验结果表明: 1、在本试验浓度范围内,叶酸浓度与乳腺癌患者及其对照个体淋巴细胞遗传损伤之间存在显著的负相关(r=-0.248~-0.832,p0.0001):叶酸在30nM时,遗传损伤均显著高于120nM及240nM (p0.001～0.05):而120nM及240nM两测试组之间未观察到各指标间的统计学差异,当叶酸升至120nM时,遗传损伤降到最低,提示在本试验条件下,120nM的叶酸是防范人类淋巴细胞遗传损伤的最
[Abstract]:Folic acid is an important micronutrient in the normal development of human body. It involves the synthesis of dUMP to dTMP.Synthesis of methionine (Met) from homocysteine (HC1) and synthesis of S- adenosine methionine (SAM)The DNA methylation was affected by the process of DNA methylation.So, folic acid, vitamin B, and Met/SAM.Blocked synthesis can cause dUMP accumulation and incorporation into DNA, resulting in various DNA structural damage.It can affect the process of DNA methylation in cells, thus affecting gene expression and chromosome separation.In this study, cytoplasmic block micronucleus analysis (CBMN) was used to study the effects of folic acid on the maintenance of breast cancer.The effects and differences of genomic stability of lymphocytes in control individuals were discussed, and the weight of folic acid metabolism pathway was also discussed.Lack of lymphocytes in breast cancer patients with BRCAI mutation and normal human lymphoid cellsGenotoxic effect of Barr cell line.In this study, lymphocytes were isolated from peripheral blood of 24 breast cancer patients and 30 normal controls.Study on the RPMI-1640 medium of 30nMN 120nM 240nM folic Acid with 8% Dialysis calf Serum 100 UThe cells were blocked by cytochalasin B (CBB) on the 8th day after culture with double antibody 2mm glutamine (pH7.0).Cells were harvested after 28 hours of cytokinesis, and CMBN was used to analyze the effects of folic acid deficiency on human lymphocyte production.Toxic effect: in order to confirm the effect of Metabac 12) on folic acid metabolism and genetic stability, the experiment also used 1550.渭 M Met and 751200pM BX 12) 12 kinds of RPMI-1640 medium containing 8% dialyzed calf serum.100U double antibody 2mm glutamine, pH7.0, cultured with BRCAI, gene mutation in breast cancer patientsLymphoblast cell line GM13705 and normal human lymphoblast cell line GM12593 were treated with cytochalasin on the 8th day.After 28 hours of blocking cytokinesis, the cells were harvested by BCBC, and CMBN analysis was used to analyze the effect of BCBI on human.Effect of Genomic Stability of Lymphocyte strain.The results show that:1. In the range of concentration in this study, folic acid concentration and genetic damage of lymphocytes in breast cancer patients and their controlsThere was a significant negative correlation between injury and injury: folic acid was inherited in 30nM.The damage was significantly higher than that of 120nM and 240nM (P 0.001 0. 05). 120nM and 240nM were the two tests.There was no statistical difference between the two groups. When folic acid rose to 120nM, the genetic damage decreased toThe results suggest that the folic acid of 120nM is the most important to prevent genetic damage of human lymphocytes.
【学位授予单位】：云南师范大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：Q987

【参考文献】